The presence of higher order cortical dysfunction in schizophrenia has been suggested previously and supported by findings from biochemical, structural, and psychopharmacological studies. However, the significance and exact nature of the abnormalities observed is unknown. Further, it is unclear whether an association exists between different measures of cortical impairment suggesting homogeneous subtypes of schizophrenia by etiology or pathophysiology. The combined methods of MRI/MRS offer the opportunity to study the presence, biological importance and relationship of anatomic functional cortical abnormalities in schizophrenia. Several lines of evidence implicate abnormalities of the temporo-limbic network in the etiology of schizophrenia, and the specific aim of this study is to apply MRI/MRS techniques and neurocognitive testing to evaluate temporal lobe function in schizophrenics and controls. In a recent pilot study completed at this Center, we applied the combined technologies of MRl/MRS in an attempt to study the relationship between quantifiable morphological characteristics and concentrations of key metabolites in the temporal lobes of schizophrenic patients. The study results indicated a reduced ratio of gray matter volume to temporal lobe volume bilaterally, as well as a decrease in the ratio of N- acetylaspartate to creatine (NAA/Cr) bilaterally in schizophrenic patients compared to normal controls. Previous studies have indicated that NAA concentration may reflect neuron integrity, and our preliminary results suggest that NAA concentration may be correlated with gray matter volume in normal controls. However, data on schizophrenic patients are heterogeneous, suggesting some patients with reduced NAA do not have accompanying lower gray matter tissue volume. The goal of the current study is to identify subgroups of schizophrenic patients who are homogeneous with regard to measures of temporal lobe structure and function. The study is unique in that it will consider MRI and MRS findings in conjunction with cognitive data so that three independent assessments of brain integrity within the same individuals will be examined while MRI is an established tool for the investigation of brain morphology, the related technology of MRS is not yet fully integrated into biological psychiatry. The proposed application of MRS techniques provides a new method of collecting biochemical information complementary to both the anatomical results provided by the MRI and the behavioral data evaluated by neuropsychological testing.